Characteristics of Choanal Atresia in Patients With Congenital Anomalies: A Retrospective Study

Introduction Choanal atresia (CA) is an uncommon congenital anomaly. There are various syndromes that are associated with CA. The purpose of this study is to determine the differences in CA's presentation and outcome when associated with other congenital anomalies and syndromes. Method This is a retrospective review study of all children (18 years and younger) who underwent CA repair in a tertiary referral healthcare center from January 2005 to April 2022. Demographics, comorbidities, radiological testing, operative reports, and outpatient reports were collected. Success was determined as a child with bilateral patent choana that is able to breathe from both nostrils comfortably. Result Twenty-four patients met the criteria for inclusion in this study. Bilateral CA was present in 15 (62.5%) patients. Mixed CA was the most common variant. There were various congenital anomalies in association with CA patients who are yet to be classified into a syndrome. The most common congenital anomaly was cleft lip and palate. Bony and mixed types were significantly associated with non-syndromic patients (p<0.05). Twenty patients (83%) were diagnosed with CA at age of less than one year, and four patients were diagnosed after one year of age. There were 36 surgeries performed on 24 patients, of which 27 were endoscopic and nine were using Hugher dilator. The overall success rate for CA repair was 50%. The median number of revisions per patient was 0.5. Conclusion CA is a challenging anomaly to repair. There are various factors that influence the outcome of children with CA. Otolaryngologists should counsel the patient and their families regarding possible need for revision especially in those with other craniofacial anomalies.


Introduction
Choanal atresia (CA) is an uncommon congenital anomaly with an estimated prevalence of one in 7000 live births [1]. CA occurs when there is failure of canalization of the posterior nasal passage [2,3]. This is thought to be due to the persistence of the buccopharyngeal membrane; however, the pathogenesis of CA remains uncertain [2,3]. Multiple risk factors have been associated with CA including teratogenic medications, chromosomal anomalies, and syndromes such as CHARGE syndrome and trisomy 21 [4,5]. CHARGE syndrome is an autosomal dominant genetic disorder that was first described by Hall and Hittner. The main manifestations are coloboma, choanal atresia, and abnormal semicircular canals; other criteria include orofacial clefts and tracheoesophageal fistula [6,7].
CA could be either unilateral or bilateral, and literature suggests that the bilaterality of the disease is more likely associated with other congenital anomalies whereas unilateral CA is often an isolated anomaly [8]; furthermore, children with bilateral CA tend to present with severe airway distress and cyanosis as they are obligate nasal breathers [9]. CA is either bony in nature or a mixture of both membranous and bony, with mixed being the most common [9,10]. Our main goal is to study the associated risk factors for this disease and to highlight the anomalies associated with this disease.

Study design and setting
This is a retrospective review study in which we collected information from patients who were diagnosed with choanal atresia (CA) and followed up in a tertiary academic referral center between 2005 and 2021. We included all patients diagnosed with CA at age of less than 18 years within our study period; any patients above 18 years or not diagnosed with choana atresia or diagnosed with CA with no intervention were excluded from our study.

Data collection
Data were collected and categorized into four domains: (1) patient demographics including the age, gender, and nationality of the patients; (2) characteristics of CA including the side and type and age at diagnosis; (3) syndromic characteristics such as the type of syndrome, if any, and other congenital anomalies; and (4) intervention data, including the type of intervention, date of intervention, stenting usage, and reoperation rate, which was defined as the need to go back to the operating room for any reason related to the CA including dilation and revision surgeries.

Data analysis
Categorical variables were expressed in the form of the number and percentage, and their groups were compared using Pearson's chi-square test with Fisher's exact test. Non-normally distributed data were reported using median and range. Correlation analysis was conducted using Spearman's rank correlation coefficient for non-parametric variables.

Confidentiality and ethical approval
Ethical approval was obtained from the King Abdulaziz University Hospital Ethical Review Board (reference number: 341-21). Access to data was available only to the principal investigator. To ensure the privacy and confidentiality of participants, all identifying variables have been removed.   Out of the included patients, three (12.5%) had both cleft lip and cleft palate, while isolated cleft lip was documented among two (8.3%) patients. Two (8.3%) patients had ear anomalies, while one (4.2%) patient had congenital cataract. Nose anomalies were diagnosed among two (8.3%) patients, whereas hypothyroidism was diagnosed in one (4.2%) patient ( Table 2).

Factors associated with recurrence of choanal atresia
There was a negative correlation between the patients' age (r=-0.255, P=0.229) and recurrence of CA. There was a positive correlation between the side of CA (r=0.272, P=0.198), syndromic choanal atresia (r=0.037, P=0.863), and recurrence. In this concern, the use of mitomycin showed a positive correlation (r=0.126, P=0.557) with the recurrence of CA. The presence of congenital anomalies (r=-0.083, P=0.69) and the use of stent (r=-0.084, P=0.69) were negatively associated with recurrence of CA (Table 10).

TABLE 10: Regression analysis highlighting the correlation between study parameters and recurrence of choanal atresia
There was a statistically significant negative correlation between the age of the patients and the bilaterality of CA (r=-0.792, P<0.001), representing bilateral CA being more frequently diagnosed earlier in the patient's life. In this respect, patients with non-syndromic CA were associated with high risk of mixed type of CA (r=-0.443, P=0.03).

Discussion
This study found that majority of the population was diagnosed with bilateral CA and with mixed-type predominance. They were less frequently associated with syndromes; however, the majority had other congenital anomalies rather than isolated CA. The approximate incidence of CA is between 1:4000 and 1:10000 live births [6] and is more often unilateral [10,11]; however, most of our population had bilateral CA, which could be due to referral bias to high-complexity centers such as ours. The composition of CA was historically classified into purely membranous, purely osseous, or mixed osseous-membranous [11].
Recently, the existence of a purely mixed type has been less frequently reported [3,12]. In our study, most cases were mixed type, consistent with findings in literature [12].
Multiple syndromes and congenital anomalies are commonly found among CA patients, especially in those with bilateral disease [6]. Associated congenital anomalies were found in more than half of our sample, with cleft lip and palate being the most found; other anomalies of the airways, nose, and ear were also noted. This is of importance as thorough screening for other anomalies is important in patients with CA to diagnose and treat other associated anomalies.
In our sample, we had four patients diagnosed with syndromes, namely, Crouzons, trisomy 21, Alfie, and Treacher-Collins. These showed lower occurrence of associated syndromes than reported in literature [13].
The endoscopic technique (nasal or retropalatal), with or without powered instrumentation, offers excellent visualization with great ease in removing the bony choanae [9]. Endoscopic intervention has a success rate of 96.3% and 86.2% for unilateral and bilateral CA, respectively [14], and was used for most of our cases. The use of mitomycin C topically as an adjunct to surgically repairing choanal atresia may offer improved patency with a decreased need for stenting, dilatations, and revision surgery [15]. However, based on our results, using mitomycin C did not significantly affect recurrence rates.
Post-operative stenting has not been proven to increase the chances of surgical success [16], even though authors still recommend the placement of stents in high-risk cases such as in neonates and in cases of bilateral CA [17]. A recently published meta-analysis of 15 studies evaluating bilateral CA repair found similar surgical success rates for stented versus non-stented patients, with stent durations varying from days to months [16]. Similarly, we found that stenting did not reduce recurrence rates or improve surgical success rates significantly.
This study was limited by its retrospective nature and missing data as well as that it is a single-center study, which limits the generalizability of study findings and results in small sample sizes. Further studies could be conducted with larger sample sizes from multiple centers to improve study results.

Conclusions
CA is a challenging anomaly to repair. There are various factors that influence the outcome of children with CA. Otolaryngologists should counsel the patient and their families regarding possible co-factors and coanomalies as well as the need for revision surgeries especially in those with other craniofacial anomalies.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. King Abdulaziz University Hospital Ethical Review Board issued approval 341-21. Access to data was available only to the principal investigator. To ensure the privacy and confidentiality of participants, all identifying variables have been removed. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.